The gist of the article is that evidence of leprosy in children is quite rare in the palaeopathological literature, possibly because the characteristic bony changes seen in the disease - rhinomaxillary syndrome or facies leprosa - are more often identified as pathological in adults, whose skulls have fully formed. So the authors are presenting information on two subadults with bone changes to the skull - one from Imperial-period Italy and one from Byzantine-era (8th-9th century AD) Turkey.

The ancient Roman child comes from the necropolis of Martellona, a site that was located along the via Tiburtina, quite close to Tivoli in the Roman suburbium. Rubini reports that there are over 400 excavated graves and that the cemetery was in use from the 6th century BC through the 4th century AD. For the most part, burials were in cappuccina style, and "the site shows an economy substantially agricultural and very poor." The child in question dates to the 2nd-3rd centuries AD according to grave goods (two nearby burials were carbon dated to 193 AD +/- 25 years), and all that remains of the skeleton are the cranium, mandible, left clavicle, and first and second left ribs. Unlike the Byzantine cemetery, where two males and one female in addition to the infant showed pathognomonic characteristics of leprosy, the Roman cemetery did not present any other evidence of leprosy in the population.

Bony changes in the skull of the Roman child are considerable. There is erosive activity in the maxilla, including resorption of the area where the right central and lateral incisors would have been, and erosive activity and remodelling of the anterior nasal spine, the inferior portion of the nasal aperture, and both inferior nasal conchae. The forehead slopes backward, and there is pitting and a cloaca in the hard palate. The Byzantine child, on the other hand, has no signs of leprous lesions other than porosity of the occipital and parietals endocranially.

Important osteological changes are present in the rhinomaxillary region. The resorption of the anterior nasal spine, the enlargement and rounding of the piriform aperture and erosion of the alveolar margin accompanied by the loss of the front teeth shown in our case are the classic changes seen in leprosy referred to as facies leprosa. [...] Furthermore, the perforation of the hard palate is present. This last change is strongly pathognomonic in leprosy diagnosis. An initial examination of the Martellona sample for M. leprae DNA in the Jerusalem laboratory was unsuccessful (data not shown).

So, the bony evidence in the Roman child is suggestive of the leprous changes we normally see in adults, but the DNA test was negative. In the Byzantine child, there were no lesions indicative of leprosy, but a DNA test was positive for M. leprae. That's odd.

The findings in this study are interesting, but there are several questions that I would have raised had I reviewed this article:

What is the context of the Roman child? There are no published data from Martellona, either osteologically or archaeologically, even though it was excavated over a decade ago according to this brief mention of the cemetery. I'd never heard of the cemetery until today (which isn't surprising, since there is a considerable amount of Italian bioarchaeological literature published in ways that are hard to find in a web or library search in this country), but there are also no citations to this cemetery anywhere in the article.

Why was the Byzantine child tested for leprosy? I suspect that the association with other leprous individuals in the cemetery and the curious porosity on the endocranial surface of the skeleton led researchers to suspect leprosy. But this is not specifically remarked on in the paper. It does seem that the three adults with pathognomonic lesions were subject to DNA testing and at least one was positive for M. leprae. The case for the presence of leprosy in the Byzantine population as a whole is much stronger than the case for leprosy in the Roman population, although little is mentioned about the Byzantine population in the article.

How do we know that facies leprosa is the same in subadults as in adults? The authors note that "Today there are no literature or hospital reports on children under 4-5 years with lepromatous leprosy that show such an involvement of the bones, even in underdeveloped countries where the medical control is difficult." They further note that "studies on leprosy sufferers in the absence of drug therapy show changes in the rhinomaxillary skeletal region only after about 7-10 years from the likely date of infection. Therefore, this is the most likely reason why today children under 14 years of age with leprosy do not show significant changes in the facial bones." The Roman child has significant bony changes to the face, suggesting advanced leprosy -- so the child would have to have been infected very young, even in utero -- and still the time-frame is off. Of course, it's possible that leprosy (or this particular form) was more aggressive than it is today, but now we're just guessing.

I'm disappointed that the Roman skeleton did not provide DNA evidence of leprosy because, as the authors note, "the case of Martellona is the first case in Italy (and possibly the world) of a child under 5 years of age with a clear rhinomaxillary syndrome." And so I'm skeptical about Rubini and colleagues' conclusions with respect to the Roman child because:

The skeleton is incomplete. After all, it was just a head. Who knows what lesions may have been on the postcranial skeleton and how those lesions may have affected a differential diagnosis?

There is a complete lack of contextual information about the population. Did other skeletons have evidence of leprosy? Tuberculosis? Other conditions considered in the differential?

There is no DNA evidence of M. leprae.

The Byzantine case is a bit more straightforward, though, leading the authors to write:

The case from Kovuklukaya displays no pathognomonic bone changes for leprosy but the palaeopathology is consistent with a chronic inflammatory response and specific PCR is positive for M. leprae DNA. We believe that this is the youngest individual in the world known to have had leprosy in the past. In sum, this study suggests that skeletal changes on young children must be analyzed in detail and aDNA analysis should be applied on subadult individuals, especially those who have non-specific infectious lesions, who are in populations with adult individuals with pathognomonic lesions of leprosy.

This conclusion is very interesting, and I think Rubini and colleagues are right to suggest that, with the current availability of biochemical analysis, testing subadults in a population with known evidence of leprosy is a key path forward in understanding the prevalence of the disease in the past. I'm not convinced yet that this Roman child had leprosy -- the differential didn't sell me on that diagnosis -- but I'm also not an expert on the disease.

I hope to hear more about the Martellona cemetery, particularly what sorts of pathologies other individuals in the population suffered from, in the future. It could be a very interesting comparison site to the Imperial-era cemeteries that have been published from the Roman suburbium.

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comments:

What does 'no DNA evidence for leprosy' mean here? That they didn't test for it, or they tested, but didn't find any? (I'm not an archaeologist or geneticist so I have no sense of how likely a false negative would be in this case.)

As far as I understand it, they did test the Roman sample for M. leprae, but it was "unsuccessful." They didn't show their data, though, and didn't discuss the possibility of a false negative.

So my statement that "There is no DNA evidence of M. leprae" means that DNA specific to M. leprae was not found on the skeletal sample that they analyzed. It's possible that testing another piece of bone or tooth would find M. leprae, but it's not clear if further tests will be done along these lines.

Great article! I just wanted to mention that evidence of leprosy is rare in literature overall because leprosy is typically a soft tissue disease until it progresses into something much nastier and involving bone tissue.

As to the comments regarding the fuzzy "no DNA evidence for leprosy", in cases like this paleopathologists usually try to hybridize complementary DNA to whatever available DNA is found on/in the body. In this case, perhaps the DNA was too degraded for hybridization or didn't exist at all.

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is a bioarchaeologist and assistant professor at the University of West Florida. This is her personal blog about archaeology, bioanthropology, and the classical world. Follow her on Twitter (@DrKillgrove) or G+, or follow PbO on Facebook.